IgG4-associated disease with systemic lupus erythematosus: A case report and review.

We report a 67-year-old man who presented with poor dietary intake and fatigue. Laboratory tests showed leukopenia, antinuclear antibody (ANA) positivity, anti-dsDNA antibody (A-dsDNA) and anti-Smith antibody (anti-Sm) negativity, decreased C3 and C4, elevated serum immunoglobulin G (IgG), IgG4, and creatinine, and 1.25 g urinary protein at 24 hours. As his condition worsened, re-examination showed thrombocytopenia and A-dsDNA positivity, and renal biopsy pathology showed IgG4-related tubulointerstitial nephritis. The final diagnosis was IgG4-related disease (IgG4-RD) with systemic lupus erythematosus (SLE). His condition improved with glucocorticoid (GC) combined with hydroxychloroquine (HCQ) and mycophenolate mofetil (MMF) treatment. This case highlights that IgG4-RD and SLE may occur successively or co-exist and may convert into each other.

microRNA-16-5p suppresses cell proliferation and angiogenesis in colorectal cancer by negatively regulating forkhead box K1 to block the PI3K/Akt/mTOR pathway.

MicroRNAs (miRNAs/miRs) have aroused increasing attention in colorectal cancer (CRC) therapy. This study is designed for a detailed analysis of the roles of miR-16-5p and forkhead box K1 (FOXK1) in cell angiogenesis and proliferation during CRC in addition to their underlying mechanisms. CRC tissues and colon cancer cell lines (SW620 and HCT8) were investigated. qRT-PCR and Western blot were utilized to evaluate miR-16-5p and FOXK1 expression. Following gain- and loss-of-function assays on miR-16-5p or FOXK1, the effects of miR-16-5p and FOXK1 were assessed on cell angiogenesis and proliferation in CRC cells. A dual-luciferase reporter assay was employed to evaluate the binding relationship of miR-16-5p and FOXK1. Western blot was used to determine the effects of miR-16-5p and FOXK1 on key molecules of the PI3K/Akt/mTOR pathway. Highly expressed FOXK1 and lowly expressed miR-16-5p were observed in CRC cells and tissues. miR-16-5p overexpression or FOXK1 knockdown reduced CRC cell proliferation and angiogenesis of human umbilical vein endothelial cells co-cultured with the supernatant of CRC cells, whereas miR-16-5p silencing or FOXK1 upregulation caused opposite trends. Additionally, miR-16-5p negatively modulated FOXK1 expression. The blockade of the PI3K/Akt/mTOR pathway was triggered by miR-16-5p overexpression or FOXK1 silencing. In conclusion, miR-16-5p hampers cell angiogenesis and proliferation during CRC by targeting FOXK1 to block the PI3K/Akt/mTOR pathway.

Hierarchical Bi2MoO6 microsphere photocatalysts modified with polypyrrole conjugated polymer for efficient decontamination of organic pollutants.

To effectively degrade organic pollutants in wastewater, visible-light-driven Bi2MoO6/PPy hierarchical heterogeneous photocatalysts were prepared through a solvothermal method and the following in-situ chemical oxidation polymerization. Compared with pristine Bi2MoO6 photocatalyst, the composite photocatalysts exhibited dramatically improved photocatalytic activity and photostability towards the degradation of methylene blue dye and tetracycline antibiotic. Bi2MoO6/PPy-80 sample achieved the highest photocatalytic degradation rates for methylene blue dye (93.6%) and tetracycline antibiotic (88.3%) under visible light irradiation. These two organic pollutants could be completely degraded into nontoxic small molecules according to in-depth HPLC-MS analysis of degradation products. The transient photocurrent responses, electrochemical impedance spectra, and photoluminescence spectra demonstrated that the introduction of PPy nanoparticles on the surface of Bi2MoO6 nanosheets could effectively accelerate the separation of photo-generated electron-hole pairs. Furthermore, a possible synergetic photocatalytic mechanism was put forward based on the electron spin resonance and XPS valence-band spectra. This work indicated that construction of hierarchical composite photocatalysts combining polypyrrole conductive polymer and Bi2MoO6 semiconductor in nanoscale is an efficient approach to improve photocatalytic activity for environmental remediation.

Inositol-Requiring Kinase 1 Regulates Apoptosis via Inducing Endoplasmic Reticulum Stress in Colitis Epithelial Cells.

BACKGROUND: Endoplasmic reticulum stress (ERS) has been studied as critical factor during occurrence and development of ulcerative colitis (UC). However, the role of ERS in inflamed UC remains unclear. AIMS: The purpose of this study was to analyze the role of inositol-requiring kinase 1 (IRE-1), a major regulator of ER, in regulating ERS and cell viability. METHODS: In UC mucosa tissue, IRE-1, BiP, XBP-1s, CHOP caspase-12 and GADD34 mRNA were assayed by qRT-PCR. Then, human normal colon epithelial cell line (NCM-460) and colon fibroblast cell line (CCD-33Co) were cultured, and downregulated or upregulated IRE-1 expression. ERS was induced with 100 ng/mL of Interleukin 6 (IL-6). CCK8 assay was performed to analyze cell proliferation. Flow cytometry analysis was conducted to detect the apoptosis. Western blot assay was used to examine ERS markers. RESULTS: IRE-1, BiP, XBP-1s, caspase-12 and CHOP mRNA were highly expressed in UC mucosa tissue, and the expression of GADD34 mRNA significantly decreased. These results show that ERS-induced unfolded protein response was enhanced in UC mucosa tissue. In cells, silencing the expression of IRE-1 could suppress cell proliferation and promote apoptosis through activating unfolded protein response, while the over-expression of IRE-1 had the opposite effect. IL-6 could induce ERS and cells apoptosis. Furthermore, we demonstrated that shRNA IRE-1 could enhance the inhibition of IL-6 on cells viability. CONCLUSIONS: Inhibition of IRE-1 enhanced unfolded protein response and cells apoptosis and IL-6-induced ERS and suggested that IRE-1 might be a potential target of UC.

Histogram analysis with computed tomography angiography for discriminating soft tissue sarcoma from benign soft tissue tumor.

To investigate the feasibility of histogram analysis with computed tomography angiography (CTA) in distinguishing between soft tissue sarcomas and benign soft tissue tumors. Fourty nine patients (23 men, mean age = 44.3 years, age range = 25-64) with pathologically-confirmed soft tissue sarcoma (n = 24) or benign soft tissue tumors (n = 25) in the lower extremities undergoing CTA for tumor evaluation were retrospectively analyzed. Two radiologists separately performed histogram analyses of CT density with CTA images by drawing a region of interest (ROI). The 10th (P10), 25th (P25), 50th (P50), 75th (P75), 90th percentiles (P90), mean, and standard deviations (SD) of measured tumor density were obtained along with measurements of the absolute value of kurtosis (AVK), absolute value of skewness (AVS), and inhomogeneity for each tumor. Intra-class correlation coefficients (ICC) were calculated to determine inter- and intra-reader variability in parameter measurements. The Mann-Whitney U test was used to compare histogram parameters between soft tissue sarcomas and benign soft tissue tumors. Receiver operator characteristic (ROC) curves were constructed to evaluate the accuracy of tumor discrimination. ICC was greater than 0.7 for AVS, AVK, and inhomogeneity, and >0.9 for mean, SD, and all percentile measures. There was no significant difference in P10, P25, P50, P75, P90, mean, or SD between soft tissue sarcomas and benign tumors (P > .05). AVS, AVK, and inhomogeneity were significantly higher in soft tissue sarcomas (P < .05). Areas under the curve (AUC) were 0.81, 0.83, and 0.84 for AVS, AVK, and inhomogeneity respectively. AUC were below 0.6 for mean, SD, and all percentiles.Skewness, kurtosis, and inhomogeneity measurements derived from histogram analysis from CTA distinguish between soft tissue sarcomas and benign soft tissue tumors.

Effect of ethylene glycol and its derivatives on the aggregation properties of reactive Orange 13 dye aqueous solution.

The aggregation behavior of dyes especially in the dyeing and printing of different textile materials is an important phenomenon which affects the process of dye adsorption and diffusion. In order to avoid the aggregation of dyes, scientists are looking for materials which can inhibit the aggregation process by fabricating the dye solution. Organic solvents have found important influence in the aggregation of dye molecules. Therefore, herein, we report the fabrication of reactive orange 13 dye solutions with the aid of ethylene glycol and its derivative organic solvents to investigate the aggregation behavior of dye molecules by UV-vis absorption spectrum, fluorescence spectrum, surface tension, rheological and particle size measurements. IR spectra were performed to understand the effect of hydrogen bonding on the aggregation behavior of dye molecules. Moreover, transmission electron microscopy was also tested to confirm the effect of organic solvents on the surface morphology of dye molecules. The results show that the reactive Orange 13 dye molecules show aggregation in terms of dimeric and multimeric structures at high dye concentrations due to π-π interaction of naphthalene rings. Moreover, on introducing the ethylene glycol and its derivatives, the dye molecules disaggregate by hydrophobic interactions of dye molecules and organic solvents which destroyed the ice-like structure between the dye molecules and the water molecules. Among the three organic solvents, DME solvent caused more disaggregation of reactive Orange 13 dye molecules due to extra hydrophobic methyl groups in its structure. The results also show that the interaction between Orange 13 dyes and ethylene glycol and its derivatives could decrease the surface tension and particle size of the dye, and increase the quantum yield and viscosity. This research will help to understand the aggregation behavior of dyes and help the textile industries to choose the suitable formulations of dye solutions for coloration of different textile substrates via dyeing and printing methods.

Intravoxel incoherent motion diffusion MR and diffusion kurtosis imaging for discriminating atypical bone metastasis from benign bone lesion.

OBJECTIVES: To investigate the feasibility of intravoxel incoherent motion (IVIM) diffusion MR and diffusion kurtosis imaging (DKI) in discriminating atypical bone metastasis from benign bone lesion in patients with tumors. METHODS: Patients with bone lesions in lower extremity suspected of metastases were enrolled in this prospective study. IVIM diffusion MR and DKI were performed before biopsy. Apparent diffusion coefficient (ADC), true diffusion (D), perfusion fraction (f) and perfusion-related pseudodiffusion (D*) were generated with IVIM, while mean kurtosis (MK) and mean diffusion (MD) generated with DKI. Two radiologists blinded to pathology results separately measured these parameters for each lesion through drawing region of interest. Intraclass correlation coefficient was used to determine the inter-reader viability in measurement. The patients with pathology-confirmed metastasis or benign lesion were analyzed. The Mann-Whitney test was used to compare IVIM and DKI parameters between metastasis group and benign lesion group. Receiver operating characteristic curves were constructed to evaluate the ability of discrimination. RESULTS: Bone lesions from 28 patients (metastasis, n = 15; benign lesion, n = 13; mean age = 55 years; age range, 34~77) were analyzed with IVIM and DKI. Intraclass correlation coefficient was greater than 0.8 for all parameters. ADC, D and MD were significantly lower in metastases versus benign lesions (p <0.05). MK and f value were significantly higher in metastases versus benign lesions (p<0.05). D* was not significantly different between the two groups (p>0.05). Areas under curve for ADC, D, f, MK and MD were 0.935, 0.939, 0.891, 0.840 and 0.844 respectively. CONCLUSIONS: IVIM and DKI derived parameters distinguish between atypical bone metastasis and benign bone lesion in selected patients with tumors. ADVANCES IN KNOWLEDGE: Bone metastasis and benign bone lesion differ in water molecular diffusion. Intravoxel incoherent motion derived true diffusion distinguishes between atypical bone metastasis and benign lesion.

Facile fabrication of redox/pH dual stimuli responsive cellulose hydrogel.

A cellulose-based multi-responsive hydrogel was prepared by the facile incorporation of enamine and disulfide bonds in the same system at physiological pH. The cellulose hydrogel was obtained by simply mixing aqueous solutions of cellulose acetoacetate (CAA) and cystamine dihydrochloride (CYS) at room temperature. The internal morphology, structure, and mechanical properties of the cellulose hydrogel were characterized by scanning electron microscopy (SEM), Fourier transform infrared (FTIR) and Raman spectroscopies, nuclear magnetic resonance (NMR), and water retention, porosity, and rheology measurements. The cellulose hydrogel showed reversible sol-gel transitions in response to both pH and redox triggers. In addition, it displayed good stability under physiological conditions. Gels loaded with small molecules showed variable release properties in response to pH or redox stimuli. The preparation protocol presented here could be used to fabricate other multi-responsive polysaccharide hydrogels.

RUFY3 interaction with FOXK1 promotes invasion and metastasis in colorectal cancer.

RUFY3 is highly expressed in brain tissue and has a role in neuronal development. Transcriptional factor FOXK1 is involved in cell growth and metabolism. We knew that RUFY3 or FOXK1 has been correlated with the malignant of tumor cells. However, the role of these molecules in colorectal cancer (CRC) progression remains unknown. We investigated the protein expression levels by Western blot, immunofluorescence and immunohistochemistry analyses. The migration and invasive abilities of CRC cells were assessed using shRNA-mediated inhibition in vitro and in vivo. We showed that RUFY3 expression was up-regulated in CRC compared with its expression in a normal human colon cell line (FHC). RUFY3 suppression inhibited anchorage independent cell tumorigenesis. RUFY3 induced elevated expression of eight major oncogenes. Moreover, RUFY3 physically interacts with FOXK1 in CRC. A positive correlation was observed between the expression patterns of RUFY3 and FOXK1. Furthermore, RUFY3 and FOXK1 expression were correlated with tumor progression and represented significant predictors of overall survival in CRC patients. SiRNA-mediated repression of FOXK1 in RUFY3-overexpressing cells reversed the epithelial-mesenchymal transition (EMT) and metastatic phenotypes. In vivo, FOXK1 promoted RUFY3-mediated metastasis via orthotopic implantation. These findings suggest that the RUFY3-FOXK1 axis might promote the development and progression of human CRC.

Facile synthesis of cellulose derivatives based on cellulose acetoacetate.

In the present work, cellulose acetoacetates (CAA) was used as a precursor for preparing diversely functionalized cellulose derivatives. Four amino-bearing compounds, namely hexylamine (HA), l-glutamic acid (Glu), cysteine (Cys), and tyramine (TA) were reacted with acetoacetyl groups providing alkyl-, carboxyl-, thiol-, or phenolic functionalized cellulose. The reaction was conducted under mild conditions without catalysts and UV light. The products were characterized with FT-IR, NMR and solubility measurement. 1H NMR measurement demonstrated the conversion of acetoacetyl groups were ideal, and all the cellulose derivatives demonstrated good solubility in certain solvent. Besides, CAA held a good stability under room temperature. This approach offers broad possibilities for developing new cellulose based materials. Moreover, this protocol can also be applied to fabricate other polysaccharide derivatives.

Overexpression of Srcin1 contributes to the growth and metastasis of colorectal cancer.

The adaptor protein Srcin1 is a novel Src-binding protein that regulates Src activation through C-terminal Src kinase (Csk). Srcin1 behaves as a tumour suppressor in breast cancer, but the role of Srcin1 in the development of colorectal cancer (CRC) remains unknown. In the present study, Srcin1 expression in normal tissue was examined by tissue microarray and assessed by immunohistochemistry in 10 patients. In addition, the biological impact of Srcin1 knockdown on CRC cells was investigated in vitro and in vivo. The results showed that Srcin1 was expressed in different types of normal human tissues, whereas its expression was increased in human CRC tissues. Srcin1 expression also correlated with tumour progression. The suppression of Srcin1 induced cell differentiation and G0/G1 cell cycle arrest. Furthermore, Srcin1 increased cell growth as well as the capacity of migration and invasion in CRC cells. Srcin1 induced the activation of the Wnt/ß-catenin signalling pathway. Moreover, Srcin1 suppression sensitized cancer cells to 5-fluorouracil (5-FU)-induced apoptosis in vitro and in vivo. Together, these results demonstrate that Srcin1 contributes to CRC carcinogenesis, invasion and metastasis. These findings provide a rationale for a mechanistic approach to CRC treatment based on the development of Srcin1-targeted therapies.

Rufy3 promotes metastasis through epithelial-mesenchymal transition in colorectal cancer.

Rufy3 is a RUN domain-containing protein that has been associated with gastric cancers; however, the role of Rufy3 in the progression of colorectal cancer (CRC) remains unknown. We demonstrated that Rufy3 expression was higher in 11/12 fresh CRC tissues than in adjacent normal tissues. Rufy3 induced elevated expression and transactivity of four major oncogenes in CRC. Moreover, siRNA-mediated repression of Rufy3 induced G0/G1 cell cycle arrest, and Rufy3 overexpression enhanced CRC cell proliferation in vitro and in vivo. Furthermore, Rufy3 up-regulation promoted epithelial-mesenchymal transition (EMT) and metastatic phenotypes. Using an established in vitro cell model of 5-fluorouracil-resistant (5-FU) CRC cells, we assessed cellular morphology, molecular changes, and invasion and found that these characteristics were consistent with EMT. Silencing of Rufy3 by siRNA reversed EMT and greatly diminished the invasion of 5-FU-treated cells. In addition, TGF-ß1 induced Rufy3 expression in a dose-dependent manner, and Rufy3 knockdown inhibited TGF-ß1-induced EMT. In vivo, higher expression of Rufy3 promoted CRC cell invasion and metastasis and induced EMT. Taken together, this work identified that Rufy3 promoted cancer metastasis in CRC cells through EMT induction.

Direct regulation of FOXK1 by C-jun promotes proliferation, invasion and metastasis in gastric cancer cells.

Forkhead box (FOX) K1 is a member of the FOX transcription factor superfamily. High FOXK1 expression is associated with several cancers. However, whether FOXK1 expression contributes to gastric cancer (GC) development and progression remains unknown. We analyzed the FOXK1 promoter using the Promo software and found several binding sequence transcription factors, including c-jun. However, the molecular mechanism by which FOXK1 affects the c-jun-mediated malignant phenotype is poorly understood. Here, we found that FOXK1 protein expression was higher in 8/10 (80.0%) fresh cancer tissues compared with that in adjacent normal tissues. FOXK1 overexpression enhanced the proliferation, migration and invasion of GC cells. Moreover, FOXK1 expression was stimulated by transforming growth factor-ß1 (TGF-ß1). FOXK1 acted as a potential epithelial-to-mesenchymal transition (EMT) inducer by stimulating vimentin expression and inducing the loss of E-cadherin in stable FOXK1-transfected cells. The results of promoter reporter and chromatin immunoprecipitation assays demonstrated that c-jun directly binds to and activates the human FOXK1 gene promoter. A positive correlation was observed between the expression patterns of FOXK1 and c-jun in GC cells and tissue. FOXK1 and c-jun expression were correlated with tumor progression and represented significant predictors of overall survival in GC patients. However, the siRNA-mediated repression of c-jun in FOXK1-overexpressing cells reversed EMT, as well as the proliferative and metastatic phenotypes. In vivo, c-jun promoted FOXK1-mediated proliferation and metastasis via orthotopic implantation. The evidence presented here suggests that FOXK1-directed regulation by c-jun promote the development and progression of human GC.

Knockdown of FOXK1 alone or in combination with apoptosis-inducing 5-FU inhibits cell growth in colorectal cancer.

Forkhead box K1 (FOXK1) is a member of the FOX transcription factor family, which plays an important role in oncogenesis. However, the exact function and mechanism of FOXK1 in human colorectal cancers (CRCs) remain unclear. In the present study, we first screened for potential FOXK1 target genes by ectopically expressing FOXK1 in SW480 cells and examined the subsequent changes in the expression levels of major oncogenes using RT-PCR. We also evaluated the effects of FOXK1 regulation on growth and apoptosis. In addition, we investigated the biological impact of FOXK1 knockdown on CRC cells in vitro and in vivo. We found that FOXK1 overexpression increased the expression of multiple oncogenes in vitro. FOXK1 promoted serum-dependent and anchorage-dependent and -independent cell growth. Knockdown of FOXK1 induced G0/G1 cell cycle arrest in CRC cells. Moreover, FOXK1 suppression induced apoptosis and increased cell susceptibility to 5-fluorouracil (5-FU)-induced apoptosis. Furthermore, a xenograft model was established to explore FOXK1 shRNA-mediated tumorigenesis in vivo. A strong antitumorigenic effect of FOXK1-shRNA was enhanced when combined with 5-FU treatment. These findings implicate FOXK1 as a cell cycle and growth modulator that inhibits apoptosis in colon cancer cells. FOXK1-shRNA may serve as a novel and potent therapeutic agent, alone or with 5-FU, against colon cancer.

Oncogene FOXK1 enhances invasion of colorectal carcinoma by inducing epithelial-mesenchymal transition.

Transcriptional factor FOXK1 is a member of the FOX family, involved in the cell growth and metabolism. The higher expression of FOXK1 leads to a variety of diseases and may play an important role in the development of various tumors. However, the role of FOXK1 in the progression of colorectal cancer (CRC) remains unknown. We demonstrated that FOXK1 was overexpressed in 16 types of solid tumor tissues via tissue multi-array (TMA). We found that FOXK1 induced elevated expressions and transactivities of five major oncogenes in CRC. Moreover, the elevated expression of FOXK1 was showed to be correlated with tumor progression and was a significant predictor of overall survival in CRC patients. Furthermore, it was showed that the depletion of FOXK1 expression could inhibit the migratory and invasive abilities of CRC cells. In contrast, ectopic expression of FOXK1 elicited the opposite effects on these phenotypes in vitro. FOXK1 promoted tumor metastasis through EMT program induction. In addition, TGF-ß1 induced FOXK1 expression in a time-dependent pattern and the knockdown of FOXK1 inhibited TGF-ß1-induced EMT. In vivo, higher expression of FOXK1 promotes CRC cell invasion and metastasis, and induces EMT in CRC as well. Alltogether, it was concluded that the higher expression of FOXK1 could indicate a poor prognosis in CRC patients since that FOXK1 induces EMT and promotes CRC cell invasion in vitro and in vivo.

HIF-1α Promotes Epithelial-Mesenchymal Transition and Metastasis through Direct Regulation of ZEB1 in Colorectal Cancer.

It is well recognized that hypoxia-inducible factor 1 alpha (HIF-1α) is involved in cancer metastasis, chemotherapy and poor prognosis. We previously found that deferoxamine, a hypoxia-mimetic agent, induces epithelial-mesenchymal transition (EMT) in colorectal cancer. Therefore, here we explored a new molecular mechanism for HIF-1α contributing to EMT and cancer metastasis through binding to ZEB1. In this study, we showed that overexpression of HIF-1α with adenovirus infection promoted EMT, cell invasion and migration in vitro and in vivo. On a molecular level, HIF-1α directly binding to the proximal promoter of ZEB1 via hypoxia response element (HRE) sites thus increasing the transactivity and expression of ZEB1. In addition, inhibition of ZEB1 was able to abrogate the HIF-1α-induced EMT and cell invasion. HIF-1α expression was highly correlated with the expression of ZEB1 in normal colorectal epithelium, primary and metastatic CRC tissues. Interestingly, both HIF-1α and ZEB1 were positively associated with Vimentin, an important mesenchymal marker of EMT, whereas negatively associated with E-cadherin expression. These findings suggest that HIF-1α enhances EMT and cancer metastasis by binding to ZEB1 promoter in CRC. HIF-1α and ZEB1 are both widely considered as tumor-initiating factors, but our results demonstrate that ZEB1 is a direct downstream of HIF-1α, suggesting a novel molecular mechanism for HIF-1α-inducing EMT and cancer metastasis.